Despite the widespread and persistent clinical need for non-invasive prenatal diagnosis of common chromosome abnormalities, methods to perform such diagnoses are not currently available. Recent work showing the feasibility of obtaining fetal DNA from non-invasive samples of maternal blood as well as from the uterine cervix offers an attractive avenue through which non-invasive prenatal diagnosis might be performed. However, the routine use of non-invasively obtained samples remains elusive because the fetal DNA exists in a mixture with a high proportion of "contaminating" maternal DNA, making it challenging to detect fetal specific sequences. We have developed novel method that makes use of differential methylation to allow for the selective amplification of trophoblast-specific sequences from mixtures that contain a high proportion of non- trophoblast DNA. We hypothesize that this method can be used in conjunction with other technologies to diagnose chromosome abnormalities using DNA derived from non-invasive sources such as maternal plasma or maternal cervical samples. The overall goals of the work proposed in this application are to 1) provide a large-scale "catalog" of trophoblast specific DNA segments that can be amplified by our method and 2) to explore the feasibility of two different methods by which selectively amplified fetal DNA segments might be used for non-invasive detection of fetal aneuploidy. We anticipate that the achievement of these aims will pave the way to the development of new, non-invasive prenatal tests for fetal aneuploidy. When and if such methods become available, they will revolutionize prenatal diagnosis and will represent a major milestone in the improvement of prenatal care.